The immature mammalian kidney is characterized by anatomical glomerular preponderance and has been represented as capable only of maintaining a marginal balance in conserving fluid and electrolytes for the metabolic requirements of the actively growing animal. Early studies supported this concept by finding low ratios of maximal rates of tubular reabsorption of glucose (TmG), of maximal tubular transport of para-aminohippurate (TmPAH), of clearances of PAH and of maximal rates of tubular reabsorption of phosphate to glomerular filtration rates. More recently, however, it has been noted that glomerulo-tubular (GT balance obtains for sodium and water in the kidneys of dogs, guinea pigs and rats after birth, and the renal handling of glucose is quite mature at birth in humans and dogs. It has been reported that tubular maturation of the immature kidney can be stimulated by penicillin therapy, by increasing functional demands and by reducing nephron mass, but only during periods of rapid growth characteristically in the fetus and newborn animal. Phenobarbital given to newborns stimulates hepatic clearance of organic anions from plasma by increasing the liver content of Y protein, a substance found also in renal tubules. The waking puppy will be used as the experimental model from birth to 6 weeks of age to more adequately define functional GT relationships in the newborn. Nephrogenesis continues post-natally in the dog for 2-3 weeks, a period similar to human kidney development prior to birth. Inulin, glucose and PAH will be used to define normal patterns of glomerular and tubular functions, functional nephron heterogeneity and GT relationships as functions of age. Once functional patterns are established, the effect of penicillin, PAH and phenobarbital given to pregnant bitches and later to puppies will be examined. Finally, chronic hyperglycemia and uninephrectomy at birth will be studied to determine the effect of increased functional load on GT relationships for the developing kidney. The hypothesis to be tested is that although low at birth, glomerular and tubular functions increase with age and GT balance is preserved even during periods of rapid structural and functional change.